1. Field of the Invention
The discovery of the pentapeptide opiate agonists, leu-enkephalin and met-enkephalin offered the opportunity of new analgesics based on amino acids, which might avoid addiction and the other side effects encountered with morphine, its derivatives and synthetic analogs. There has therefore been an intensive effort to develop new low molecular weight polypeptides which would act as opiate agonists without the previously encountered side effects of opiate analgesics, which could be used at low dosages, would not be rapidly degraded in vivo, and would be capable of crossing the blood-brain barrier.
2. Brief Description of the Prior Art
A number of references teach a variety of enkephalin analogs. See for example Hughes, et al., Nature 258 577 (1975); Chang, et al. Life Sciences, 18, 1473 (1976); and Coy, et al. Biochem. Biphys. Res. Comm., 73, 632 (1976).